Misoprostol is a compound of the formula ##STR1## Misoprostol is classified in a group of compounds generally known as prostaglandins. Prostaglandins exhibit a variety of beneficial biological responses and therefore are useful as pharmaceutical agents. In particular misoprostol is a known inhibitor of gastric acid secretion and is also known to possess mucosal protective properties. Misoprostol, as a pharmaceutical agent, is therefore useful in preventing gastric ulcers.
Generally, prostaglandins are difficult to formulate into stable pharmaceutical dosage forms because of their relative instability. Prostaglandins tend to decompose above room temperature and in the presence of small amounts of acid, base or water. For example, at 55.degree. C., 75% of the prostaglandin, misoprostol, degrades in 4 weeks. The problem to be addressed in developing prostaglandin formulations has been how to stabilize the prostaglandin without loss of pharmacological activity. Various attempts have been made at stabilizing prostaglandins for use in pharmaceutical dosage forms.
U.S. Pat. No. 4,301,146 discloses solid state dispersions of misoprostol, a prostaglandin derivative in hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP) in combination with other tablet and capsule excipients.
Complexation with various cyclodextrins has been used to stabilize various prostaglandins. See for example Inaka et al., J. Inclusion Phenomena, 2:467-474 (1984)!. U.S. Pat. No. 4,113,882 describes the use of lyophilized compositions containing, dextran, dextrin, thiol compounds, a lower alkylcellulose or deoxycholic acid salts for stabilization of PGE type compounds. JP 53050141 describes a tricaprylin solution as a relatively stable media for PGE2. DE 2515001 describes a freeze-dried powder, containing polyvinylpyrrolidone (PVP) as a stable media for PGE.sub.2. JP 53148518 describes freeze-dried bentonite as a stable media for PGE.sub.2. JP 53130417 describes freeze-dried starch as a stable media for PGE.sub.2. JP 60169430 describes various preservatives and antioxidants in coconut oil as a stable media for a PGE.sub.1 derivative. EP 260719 describes the use of polyvinylacetate in the stabilization of PGE.sub.2. Yalkowski et al. J. Pharm. Sci., 68:114-115 (1979)! describe the use of triacetin in the stabilization of a PGE.sub.2 derivative.
Due to the usefulness of prostaglandins as pharmacological agents and because of their instability in pharmaceutical dosage forms, there is a continuing need for stabilizing prostaglandins, including misoprostol, for use in pharmaceuticals. The present invention provides stabilized amorphous solid state dispersions of misoprostol, which formulations can be used in preparing pharmaceutical dosage forms.